NM_000444.6(PHEX):c.2239del (p.Arg747fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 20, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001214030.7

Allele description [Variation Report for NM_000444.6(PHEX):c.2239del (p.Arg747fs)]

NM_000444.6(PHEX):c.2239del (p.Arg747fs)

Genes:

PTCHD1-AS:PTCHD1 antisense RNA (head to head) [Gene - HGNC]
PHEX:phosphate regulating endopeptidase X-linked [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xp22.11

Genomic location:

Preferred name:

NM_000444.6(PHEX):c.2239del (p.Arg747fs)

HGVS:

NC_000023.11:g.22247942del
NG_007563.2:g.220139del
NM_000444.6:c.2239delMANE SELECT
NM_001282754.2:c.*74del
NP_000435.3:p.Arg747fs
NC_000023.10:g.22266058del
NC_000023.10:g.22266059del
NM_000444.5:c.2239del

Protein change:

R747fs

Links:

dbSNP: rs1936440191

NCBI 1000 Genomes Browser:

rs1936440191

Molecular consequence:

NM_001282754.2:c.*74del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000444.6:c.2239del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001385693	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 20, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9199930, 9768674, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001385693

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 20, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genomic organization of the human PEX gene mutated in X-linked dominant hypophosphatemic rickets.

Francis F, Strom TM, Hennig S, Böddrich A, Lorenz B, Brandau O, Mohnike KL, Cagnoli M, Steffens C, Klages S, Borzym K, Pohl T, Oudet C, Econs MJ, Rowe PS, Reinhardt R, Meitinger T, Lehrach H.

Genome Res. 1997 Jun;7(6):573-85. No abstract available.

PubMed [citation]

PMID:: 9199930

Mutational analysis of PHEX gene in X-linked hypophosphatemia.

Dixon PH, Christie PT, Wooding C, Trump D, Grieff M, Holm I, Gertner JM, Schmidtke J, Shah B, Shaw N, Smith C, Tau C, Schlessinger D, Whyte MP, Thakker RV.

J Clin Endocrinol Metab. 1998 Oct;83(10):3615-23.

PubMed [citation]

PMID:: 9768674

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001385693.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant disrupts the C-terminus of the PHEX protein. Another variant that disrupts this region (c.2239C>T) has been determined to be pathogenic (PMID: 9199930, 9768674). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (ExAC no frequency). This sequence change results in a frameshift in the PHEX gene (p.Arg747Aspfs*24). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3 amino acids of the PHEX protein and extend the protein by an additional 20 amino acids. This variant has not been reported in the literature in individuals with PHEX-related conditions.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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